In recent years, the development of novel anticoagulant drug, factor Xa inhibitor initiated a new direction for anticoagulant treatment. The factor Xa inhibitor not only increases the anticoagulant effect, but also reduces the risk of hemorrhage. It does not need blood monitoring, and is convenient for long-term treatment. Studies show that factor Xa plays an important role in controlling thrombin formation and activating blood coagulation cascade. Anti-coagulation effect is even stronger if the upstream factors of the coagulation cascade is inhibited. Factor Xa cannot activate platelets, and does not have positive feedback effect on the coagulation cascade. Direct factor Xa inhibitor can not only inhibit the factors associated with thrombus, but also inhibit the factors associated with prothrombin.
Rivaroxaban is the first factor Xa inhibitor on the market. Numbers of clinical research show that rivaroxaban is prior than the standard medicine Enoxaparin Sodium on preventing and treating venous thrombosis embolism. Rivaroxaban is clinically used to prevent deep venous thrombosis (DVT) and pulmonary embolism (PE) after hip and knee replacement surgery. It can prevent cerebral apoplexy and non-central nervous system embolism in patients with non-valve atrial fibrillation, reduce the risk of palindromia of coronary syndrome, and the like. However, overdosing can lead to bleeding complications due to the pharmacodynamics properties of Rivaroxaban. The bleeding risk of patients within certain sub-groups is high and specific antidote has not been developed.
Apixaban is an oral selective factor Xa activation inhibitor, a variation of Razaxaban. Developed by the collaboration of Pfizer and Bristol-Myers Squibb, it is now available on America and European Union market. It can prevent thrombus, especially for patients taken hip or knee replacement operation. However, among patients with acute coronary syndrome, researchers found that Apixaban may lead to increased dose-dependent bleeding cases and reduced ischemic cases, when applied together with anti-platelet treatment. The safety and effectiveness of Apixaban may depend on the basic anti-platelet treatment.
Edoxaban is a small molecule oral anticoagulation medicine developed by the Daiichi Sankyo in Japan. It is a blood clotting factor X (FXa) blocker and is used for treating concurrent venous thromboembolism (VTE) in patients taken total knee replacement (TKA), total hip replacement (THA) and hip fracture surgery (HFS). In the coagulation process, activated clotting factors X (FXa) activates prothrombin (FII) into thrombin (FIIa), which promotes the formation of fibrin and thrombus. Therefore, FXa has become a main target for the development of new generation of anti-coagulation medicine. Edoxaban inhibits the formation of thrombus by selectively, reversibility and directly inhibiting FXa. It is 104 times more selective to FXa compared to FIIa. Clinical studies in Japan or abroad all prove that Edoxaban can effectively and reliably inhibit concurrent VTE in patients taken lower limb orthopaedic surgery. However, its high cost is a limitation of this medicine, which may be an issue for most patients.
The relative molecular weight of Razaxaban is 528. Being as an effective oral peptide analogue, it has a high affinity with factor Xa. A phase II clinical study shows that it is effective in preventing venous thromboembolism (VTE) after orthopedic surgery. This is a random double-blind study and 656 patients taken total knee replacement operation participate. Among 438 effective patients, Razaxaban and VTE occurrence are in a dose-dependent manner. Notably, the VTE occurrence rate of patients taking Razaxaban 25 mg is significantly lower than that of patients taking enoxaparin, while the occurrence rate of large bleeding is similar between the two groups. However, patients taking Razaxaban 50-100 mg are more likely to have large bleeding compared to patients taking Enoxaparin.
Otamixaban is a thrombin factor Xa inhibitor for injection with high-selectivity and reversibility. It inhibits the formation of thrombus through a dose-dependent manner, with rapid effect-acting and loss of efficacy period. Its pharmacokinetic follows the linear pattern and is not easy to be eliminated through kidney. Previous studies show that treating ACS using activated X factor inhibitor has the risk of thrombus formation. Therefore, it should be noted in PCI operation that the dose of the anticoagulation drugs and other additional antithrombotic factors should be adjusted. However, the use of medium doses of Otamixaban appears to be free of these concerns. In addition, as Otamixaban has many advantages including rapid effect onset and loss of efficacy, intravenous administration and predictable anticoagulanting reaction (needn't monitor), Otamixaban can be the only anticoagulant medicine for NSTE-ACS patients from emergency treatment to interventional therapy, which is a great advantage. Other studies reported that Otamixaban excretion through kidney is less than 25%. Thus, the dosage for patients with impaired renal function does not need to be adjusted. It is also reported that Otamixaban cannot reduce the occurrence of ischemic cases and can increase the bleeding risk. So, it suggested not using Otamixaban on NSTE-ACS patients taking early PCI operation.
Therefore, how to reduce the massive use of Xaban medicine to reduce side effect and how to reduce the cost need to be resolved.